Evidence map›Paper›PMID 37125150›Full record

ArticleMolecular therapy. Nucleic acids2023

Lentiviral vectors for inducible, transactivator-free advanced therapy medicinal products: Application to CAR-T cells.

María Tristán-Manzano, Noelia Maldonado-Pérez, Pedro Justicia-Lirio, Marina Cortijo-Gutierréz, Pablo Tristán-Ramos, Carlos Blanco-Benítez, Kristina Pavlovic, Araceli Aguilar-González, Pilar Muñoz, Francisco J Molina-Estevez and 5 more

Open access · goldAbstract read
In one paragraph

Article in Molecular therapy. Nucleic acids, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.3field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 10 citations in OpenAlex.

  1. In Vivo T-Cell Engineering: Revolution in Delivery Strategies and Clinical Translation.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 4 institutions in 2 countries.

María Tristán-ManzanoLentiStem Biotech, Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research (GENYO), PTS, Avda. de la Ilustración 114, 18016 Granada, Spain.
Noelia Maldonado-PérezDepartment of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), PTS, Av. de la Ilustración 114, 18016 Granada, Spain.
Pedro Justicia-LirioLentiStem Biotech, Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research (GENYO), PTS, Avda. de la Ilustración 114, 18016 Granada, Spain.
Marina Cortijo-GutierrézDepartment of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), PTS, Av. de la Ilustración 114, 18016 Granada, Spain.
Pablo Tristán-RamosDepartment of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), PTS, Av. de la Ilustración 114, 18016 Granada, Spain.
Carlos Blanco-BenítezLentiStem Biotech, Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research (GENYO), PTS, Avda. de la Ilustración 114, 18016 Granada, Spain.
Kristina PavlovicDepartment of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), PTS, Av. de la Ilustración 114, 18016 Granada, Spain.
Araceli Aguilar-GonzálezDepartment of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), PTS, Av. de la Ilustración 114, 18016 Granada, Spain.
Pilar MuñozDepartment of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), PTS, Av. de la Ilustración 114, 18016 Granada, Spain.
Francisco J Molina-EstevezDepartment of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), PTS, Av. de la Ilustración 114, 18016 Granada, Spain.
Valerie GriescheDepartment of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), PTS, Av. de la Ilustración 114, 18016 Granada, Spain.
Juan Antonio MarchalInstituto de Investigación Biosanitaria ibs.GRANADA, University Hospitals of Granada - University of Granada, 18016 Granada, Spain.
Sara R HerasDepartment of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), PTS, Av. de la Ilustración 114, 18016 Granada, Spain.
Karim BenabdellahDepartment of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), PTS, Av. de la Ilustración 114, 18016 Granada, Spain.
Francisco MartinDepartment of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), PTS, Av. de la Ilustración 114, 18016 Granada, Spain.
Universidad de Granada · ESPfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research · ESGerman Cancer Research Center · DEInstituto Maimónides de Investigación Biomédica de Córdoba · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Controlling transgene expression through an externally administered inductor is envisioned as a potent strategy to improve safety and efficacy of gene therapy approaches. Generally, inducible ON systems require a chimeric transcription factor (transactivator) that becomes activated by an inductor, which is not optimal for clinical translation due to their toxicity. We generated previously the first all-in-one, transactivator-free, doxycycline (Dox)-responsive (Lent-On-Plus or LOP) lentiviral vectors (LVs) able to control transgene expression in human stem cells. Here, we have generated new versions of the LOP LVs and have analyzed their applicability for the generation of inducible advanced therapy medicinal products (ATMPs) with special focus on primary human T cells. We have shown that, contrary to all other cell types analyzed, an Is2 insulator must be inserted into the 3' long terminal repeat of the LOP LVs in order to control transgene expression in human primary T cells. Importantly, inducible primary T cells generated by the LOPIs2 LVs are responsive to ultralow doses of Dox and have no changes in phenotype or function compared with untransduced T cells. We validated the LOPIs2 system by generating inducible CAR-T cells that selectively kill CD19+ cells in the presence of Dox. In summary, we describe here the first transactivator-free, all-one-one system capable of generating Dox-inducible ATMPs.

Indexed as

advance therapy medicinal productsall-in-one lentiviral vectorsdoxycyclineexternally controlledgene therapyinducibleinducible CAR-T cellsMT: Delivery Strategiestransactivator-free

Identifiers

PMID37125150
PMCPMC10141506
OpenAlexW4361225372

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.